Evaluation of a series of bicyclic CXCR2 antagonists

  • Bioorg Med Chem Lett. 2008 Jan 15;18(2):798-803. doi: 10.1016/j.bmcl.2007.11.039.
Iain Walters  1 ,  Caroline Austin ,  Rupert Austin ,  Roger Bonnert ,  Peter Cage ,  Mark Christie ,  Mark Ebden ,  Stuart Gardiner ,  Caroline Grahames ,  Steven Hill ,  Fraser Hunt ,  Robert Jewell ,  Shirley Lewis ,  Iain Martin ,  David Nicholls ,  David Robinson
Affiliations
  • 1. Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, United Kingdom. [email protected]
PMID: 18240390 DOI: 10.1016/j.bmcl.2007.11.039
Abstract

The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antagonists with markedly improved biological and pharmacokinetic properties, which are suitable pharmacological tools to probe the in vivo effects of CXCR2 antagonism combined with the associated CCR2 activity.

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